Abstract
Background
Hyperdynamic circulation in portal hypertension (PHT) depends on central neural activation. However, the initiating mechanism that signals PHT to the central neural cardiovascular-regulatory centers remains unclear. We aimed to test the hypothesis that oxidative stress in the gut initiates the signal that activates central cardiovascular nuclei in portal hypertensive rats.
Methods
Two groups of rats were used. One had portal hypertension produced by partial portal vein ligation, while controls underwent sham operation. Hemodynamics including portal pressure, cardiac output, mean arterial pressure (MAP) and peripheral vascular resistance were measured. Activation of central cardiovascular nuclei was determined by immunohistochemical Fos expression in the paraventricular nucleus (PVN) of the hypothalamus. Myeloperoxidase activity, an oxidative stress marker, was measured in the jejunum. Hydrogen peroxide, the antioxidant N-acetyl-cysteine (NAC) or saline controls were administered for 12–14 days by gavage or osmotic minipumps placed in the peritoneal cavity.
Results
Compared with controls, PHT rats showed increased cardiac output (54.2 ± 9.5 vs 33.6 ± 2.4 ml/min/100 g BW, p < 0.01), decreased MAP (96.2 ± 6.4 mmHg vs 103.2 ± 7.8, p < 0.01) and systemic vascular resistance (1.84 ± 0.28 vs 3.14 ± 0.19 mmHg/min/ml/100 g BW, p < 0.01). PHT rats had increased jejunal myeloperoxidase and PVN Fos expression. NAC treatment eliminated the hyperdynamic circulation, decreased jejunal myeloperoxidase and PVN Fos expression in PHT rats, but had no effect on sham controls. H2O2 significantly increased PVN Fos expression and decreased MAP.
Conclusion
These results indicate that in PHT, mesenteric oxidative stress is the initial signal that activates chemoreceptors and triggers hyperdynamic circulation by central neural cardiovascular-regulatory centers.
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Data availability
Data Availability Statement: The raw data of this study can be made available upon written request to the corresponding author.
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Funding
This study was supported by the Canadian Liver Foundation operating grant RSO1019933.
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SL: study concept and design, data analysis, manuscript revision. HL: writing first draft, data collection and analysis, manuscript revision. NA, KTY, LA: data collection and analysis, revision of manuscript. All authors provided final approval of the version submitted for publication.
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Hongqun Liu, Noura Alhassan, Ki Tae Yoon, Lamees Almutlaq and Samuel S. Lee declare that they have no conflicts of interest.
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The protocols were approved by the University of Calgary, Faculty of Medicine Animal Care Committee (AC21-0206), and all animals received humane care in accordance with guidelines established by the Canadian Council on Animal Care.
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Liu, H., Alhassan, N., Yoon, K.T. et al. Oxidative stress triggers hyperdynamic circulation via central neural activation in portal hypertensive rats. Hepatol Int 17, 689–697 (2023). https://doi.org/10.1007/s12072-023-10481-5
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DOI: https://doi.org/10.1007/s12072-023-10481-5